Lokelma Potassium Reduction
Lokelma (sodium zirconium cyclosilicate) reduces serum potassium by approximately 0.7 mEq/L at 48 hours when dosed at 10 g three times daily, with greater reductions (up to 1.1 mEq/L) in patients with baseline potassium >5.5 mEq/L. 1, 2
Acute Correction Phase (First 48 Hours)
The magnitude of potassium reduction is dose-dependent and varies by baseline potassium level:
Standard dosing (10 g three times daily):
- Mean reduction of 0.7 mEq/L at 48 hours in all patients 1, 3
- Mean reduction of 1.1 mEq/L in patients with baseline potassium >5.5 mEq/L 1
- Median time to normalization: 2.2 hours, with 84% achieving normokalaemia by 24 hours and 98% by 48 hours 4
Lower doses show reduced efficacy:
- 5 g three times daily: 0.5 mEq/L reduction 1, 3
- 2.5 g three times daily: 0.5 mEq/L reduction 1, 3
- 1.25 g three times daily: 0.3 mEq/L reduction (similar to placebo) 1
Maintenance Phase (Long-term Control)
Once normokalaemia is achieved, maintenance dosing sustains potassium control:
Once-daily maintenance dosing:
- 5 g daily: maintains mean potassium at 4.8 mEq/L 4
- 10 g daily: maintains mean potassium at 4.5 mEq/L 4
- 15 g daily: maintains mean potassium at 4.4 mEq/L 4
- 80-94% of patients maintain normokalaemia during days 8-29 depending on dose 4
Clinical Context and Efficacy Across Subgroups
Lokelma demonstrates consistent efficacy regardless of comorbidities:
- Equally effective in patients with chronic kidney disease (including stages 4-5), diabetes, heart failure, and those on RAAS inhibitor therapy 1, 5, 6
- In severe CKD (eGFR <30 mL/min/1.73 m²), 82% achieved normokalaemia within 24 hours and 100% within 72 hours 6
Important Clinical Considerations
Onset and limitations:
- Onset begins at 1-2 hours, making it not appropriate for life-threatening hyperkalemia requiring emergency treatment 2
- For life-threatening hyperkalemia, use insulin/glucose, beta-agonists, or dialysis first 2
Dose-dependent adverse effects to monitor:
- Edema risk increases with dose: 2% at 5 g daily, 6% at 10 g daily, and 14% at 15 g daily 2, 7, 4
- Each 10 g dose contains 1200 mg sodium during correction phase, 400-1200 mg daily during maintenance 2, 7
- Hypokalemia occurred in 10-11% of patients on 10-15 g daily maintenance doses 4
Drug interactions:
- Lokelma binds other medications throughout the GI tract, reducing their absorption 2
- Separate administration of other oral medications by at least 2 hours
Monitoring requirements:
- Check serum potassium after one week during initiation and after dose adjustments 2
- Monitor for peripheral edema, especially with maintenance doses ≥10 g daily 2, 7
Comparative Advantage
Lokelma offers superior efficacy and safety compared to older agents: